Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
Department of Cancer Prevention and Pathology, Roswell Park Cancer Institute, Buffalo, NY, USA.
Gynecol Oncol. 2014 Feb;132(2):462-7. doi: 10.1016/j.ygyno.2013.12.024. Epub 2013 Dec 25.
We determined whether DNA methylation of repetitive elements (RE) is altered in epithelial ovarian cancer (EOC) patient tumors and white blood cells (WBC), compared to normal tissue controls.
Two different quantitative measures of RE methylation (LINE1 and Alu bisulfite pyrosequencing) were used in normal and tumor tissues from EOC cases and controls. Tissues analyzed included: i) EOC, ii) normal ovarian surface epithelia (OSE), iii) normal fallopian tube surface epithelia (FTE), iv) WBC from EOC patients, obtained before and after treatment, and v) WBC from demographically-matched controls.
REs were significantly hypomethylated in EOC compared to OSE and FTE, and LINE1 and Alu methylation showed a significant direct association in these tissues. In contrast, WBC RE methylation was significantly higher in EOC cases compared to controls. RE methylation in patient-matched EOC tumors and pre-treatment WBC did not correlate.
EOC shows robust RE hypomethylation compared to normal tissues from which the disease arises. In contrast, RE are generally hypermethylated in EOC patient WBC compared to controls. EOC tumor and WBC methylation did not correlate in matched patients, suggesting that RE methylation is independently controlled in tumor and normal tissues. Despite the significant differences observed over the population, the range of RE methylation in patient and control WBC overlapped, limiting their specific utility as an EOC biomarker. However, our data demonstrate that DNA methylation is deranged in normal tissues from EOC patients, supporting further investigation of WBC DNA methylation biomarkers suitable for EOC risk assessment.
我们旨在确定与正常组织对照相比，上皮性卵巢癌（EOC）患者肿瘤和白细胞（WBC）中的重复元件（RE）的 DNA 甲基化是否发生改变。
使用两种不同的重复元件甲基化定量测量方法（LINE1 和 Alu 亚硫酸氢盐焦磷酸测序），分析 EOC 病例和对照的正常和肿瘤组织。分析的组织包括：i）EOC，ii）正常卵巢表面上皮（OSE），iii）正常输卵管表面上皮（FTE），iv）EOC 患者治疗前后的 WBC，v）与患者人口统计学匹配的对照的 WBC。
与 OSE 和 FTE 相比，EOC 中的 RE 明显低甲基化，LINE1 和 Alu 甲基化在这些组织中呈显著直接关联。相比之下，EOC 病例的 WBC RE 甲基化明显高于对照组。患者匹配的 EOC 肿瘤和治疗前 WBC 的 RE 甲基化无相关性。
与疾病起源的正常组织相比，EOC 表现出强烈的 RE 低甲基化。相比之下，EOC 患者的 WBC 中的 RE 通常呈高甲基化状态。在匹配的患者中，EOC 肿瘤和 WBC 甲基化无相关性，提示 RE 甲基化在肿瘤和正常组织中独立控制。尽管在人群中观察到显著差异，但患者和对照组 WBC 中 RE 甲基化的范围重叠，限制了它们作为 EOC 生物标志物的特异性。然而，我们的数据表明，EOC 患者的正常组织中存在 DNA 甲基化紊乱，支持进一步研究适合 EOC 风险评估的 WBC DNA 甲基化生物标志物。
